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Repeated social subjugation in early puberty lowers testosterone levels. We used hamsters to investigate the effects of social subjugation on male sexual behavior and metabolic activity within neural systems controlling social and motivational behaviors. Subjugated animals were exposed daily to aggressive adult males in early puberty for postnatal days 28 to 42, while control animals were placed in empty clean cages. On postnatal day 45, they were tested for male sexual behavior in the presence of receptive female. Alternatively, they were tested for mate choice after placement at the base of a Y-maze containing a sexually receptive female in one tip of the maze and an ovariectomized one on the other. Social subjugation did not affect the capacity to mate with receptive females. Although control animals were fast to approach females and preferred ovariectomized individuals, subjugated animals stayed away from them and showed no preference. Cytochrome oxidase activity was reduced within the preoptic area and ventral tegmental area in subjugated hamsters. In addition, the correlation of metabolic activity of these areas with the bed nucleus of the stria terminalis and anterior parietal cortex changed significantly from positive in controls to negative in subjugated animals. These data show that at mid-puberty, while male hamsters are capable of mating, their appetitive sexual behavior is not fully mature and this aspect of male sexual behavior is responsive to social subjugation. Furthermore, metabolic activity and coordination of activity in brain areas related to sexual behavior and motivation were altered by social subjugation. [ABSTRACT FROM AUTHOR]

Abstract: The involvement of different brain regions in place- and response-learning was examined using a water cross-maze. Rats were trained to find the goal from the initial arm by turning left at the choice point (egocentric strategy) or by using environmental cues (allocentric strategy). Although different strategies were required, the same maze and learning conditions were used. Using cytochrome oxidase histochemistry as a marker of cellular activity, the function of the 13 diverse cortical and subcortical regions was assessed in rats performing these two tasks. Our results show that allocentric learning depends on the recruitment of a large functional network, which includes the hippocampal CA3, dentate gyrus, medial mammillary nucleus and supramammillary nucleus. Along with the striatum, these last three structures are also related to egocentric spatial learning. The present study provides evidence for the contribution of these regions to spatial navigation and supports a possible functional interaction between the two memory systems, as their structural convergence may facilitate functional cooperation in the behaviours guided by more than one strategy. In summary, it can be argued that spatial learning is based on dynamic functional systems in which the interaction of brain regions is modulated by task requirements. [Copyright &y& Elsevier]

Distribution of three calcium-binding proteins (CaBPr) calbindin (CB), calretinin (CR), and parvalbumin (PV) in parallel with metabolic activity (cytochrome oxidase, CO) was studied in telencephalic projection zones of the tecto- and thalamofugal visual pathways in experiments on the Horsfield's terrapin Testudo horsfieldi and the pond tortoise Emys orbicularis. It was shown that the nucleus rotundus (Rot) and dorsal lateral geniculate nucleus (GLd) terminal fields in both zones (dorsolateral region of the anterior ventricular ridge, Advrdl and dorsolateral cortex, Cxdl, respectively) were CB-immunoreactive (-ir) in the both studied turtle species. The highest density of CB-ir terminals and the focus of rotundal projections in the Advrdl core coincided precisely. The GLd terminal field in Cxdl also was CR-ir. The PV contribution to innervation of both projectional zones was much lower, especially to innervation of Cxdl from GLd. In spite of similar CB-ir innervation, the projectional field of the tectofugal pathway of Advrdl had the much higher CO activity than that of the thalamofugal pathway in Cxdl. The neurons immunoreactive to all three CaBPr types were distributed in Cxdl in different ratios in each layer. In the visual Advrdl area the overwhelming majority were PV-ir neurons, whereas CB-ir neurons were absent. The conclusion is made that in spite of the CB- and CB/CR-immunoreactivity predominates over the PV-immunoreactivity in both thalamotelencephalic pathways of the visual system, the tectofugal (rotundo-Advrdl) pathway having the higher metabolic activity. [ABSTRACT FROM AUTHOR]

Abstract: The specific brain regions and circuits involved in the acquisition and expression of contextual fear conditioning are still a matter of debate. To address this issue, regional changes in brain metabolic capacity were mapped during the acquisition and expression of contextual fear conditioning using cytochrome oxidase (CO) quantitative histochemistry. In comparison with a group briefly exposed to a conditioning chamber, rats that received a series of randomly presented footshocks in the same conditioning chamber (fear acquisition group) showed increased CO activity in anxiety-related brain regions like the ventral periaqueductal gray, the ventral hippocampus, the lateral habenula, the mammillary bodies, and the laterodorsal thalamic nucleus. Another group received randomly presented footshocks, and it was re-exposed to the same conditioning chamber one week later (fear expression group). The conditioned group had significantly higher CO activity as compared with the matched control group in the following brain regions: the ventral periaqueductal gray, the central and lateral nuclei of the amygdala, and the bed nucleus of the stria terminalis. In addition, analysis of functional brain networks using interregional CO activity correlations revealed different patterns of functional connectivity between fear acquisition and fear expression groups. In particular, a network comprising the ventral hippocampus and amygdala nuclei was found in the fear acquisition group, whereas a closed reciprocal dorsal hippocampal network was detected in the fear expression group. These results suggest that contextual fear acquisition and expression differ as regards to the brain networks involved, although they share common brain regions involved in fear, anxiety, and defensive behavior. [Copyright &y& Elsevier]

Distribution of activity of cytochrome oxidase (CO) and immunoreactivity to parvalbumin (Pv) and calbindin (Cb) was studied in the optic tectum of the pigeon ( Columba livia). In the first link of the tectofugal pathway in the central gray layer (SGC = layer 13), small amounts of the CO-active and Pv-immunoreactive (Pv-ir) cellular bodies were revealed in its internal part (sublayer 13b). Some of these neurons located along the SGC lower boundary had long dendritic processes ascending into the superficial tectum layer (SGF). In the retinorecipient SGF sublayers and particularly in neuropil of the sublayers 4 and 7, the high CO activity correlating with Pv-immunoreactivity was found. It is suggested that a great contribution to metabolic activity of these sublayers is made by the largely branching dendritic processes of Pv-ir neurons of sublayer 13b. The projectional neurons SGC located in its external part (sublayer 13a) were CO-inactive and contained Cb. They sent long dendrites into sublayer 5b; in its neuropil, the high density of Cb-immunoreactivity and a moderate CO activity were detected. Thus, the tectal link of the pigeon tectofugal visual channel consists of two components-the Pv-specific, highly metabolically active and the Cb-specific, metabolically less active ones that transduce visual information from different retino-recipient SGF sublayers. The absence of the significant amount of CO-positive bodies of projectional neurons in SGC can be due to that metabolically more active are their dendritic arborizations in the SGF sublayers. [ABSTRACT FROM AUTHOR]

Summary: Skeletal muscle dysfunction (SMD) often occurs in patients with COPD, affecting their quality of life and mitochondrion is one of the cellular organelles involved in the pathogenesis of SMD in COPD. The aim of this study was to investigate exercise capacity and mitochondria skeletal muscle oxidative processes using a pilot study, with 20 COPD patients and 10 healthy subjects, prior to and following LABA treatment. The two groups were similar for BODE (2–7) and GOLD stages (2–3), and no one was cachectic or more symptomatic. The patients were randomized according to a distribution list. The Cycle Ergometry test with tau evaluation was used to determine exercise capacity, while a skeletal muscle biopsy for cytochrome oxidase (CytOX) activity evaluation was used to determine mitochondria skeletal muscle oxidative processes. In six of the COPD treated patients the individual values of tau and CytOX activity showed inversely parallel changes with a significant relationship between the tau values and the CytOX activity. No significant differences in tau values were observed in healthy subjects. In conclusion, LABA treatment may improve skeletal muscle oxidative processes, enhancing the CytOX activity and, at least in some COPD patients, such effects could be strictly linked to the kinetic exchanges occurring at skeletal muscle level, implying an important link between the regulation of oxygen uptake, energy production and the exercise capacity of these patients. Nevertheless, further studies are required and a better understanding of the mechanism(s) underlying LABA effects might allow us to identify or unmask new therapeutic target(s) in such patients. [Copyright &y& Elsevier]

Abstract: Sex differences have been found in the spatial memory which involve several regions of the limbic system. The Morris water maze (MWM) is one of the most widely used tasks in behavioral neuroscience to explore spatial and episodic memory in rats. We evaluated the oxidative metabolic activity of the prefrontal cortex, dorsal hippocampus, anterior thalamic nuclei and mammillary region following the acquisition of a spatial working memory (WM) task in young rats (30 days) of both sexes using quantitative histochemistry of the cytochrome oxidase (COx). The rats were trained until they achieved the learning criteria in the MWM using a hidden escape platform with different daily locations, and two control groups were added to evaluate the oxidative metabolism not specific to the learning task. We found a delay in the acquisition of the WM in females. A significant decrease in COx activity was found in the prefrontal cortex in both sexes. Also, changes were found in the dentate gyrus and lateral mammillary nucleus in males, whereas females showed changes in the anterodorsal thalamus and CA3. These results suggest a sex difference in the contribution of brain limbic structures to the WM process during postnatal development. [Copyright &y& Elsevier]

A quantitative morphometric study has been carried out in human neuroblastoma SK-N-BE cells to evaluate the ultrastructural features and the metabolic efficiency of mitochondria involved in the early steps of apoptosis. In mitochondria from control and apoptotic cells cytochrome oxidase (COX) activity was estimated by preferential cytochemistry. Number of mitochondria (numeric density: Nv), volume fraction occupied by mitochondria/μm3 of cytoplasm (volume density: Vv), and average mitochondrial volume (V) were calculated for both COX-positive and -negative organelles. The ratio (R) of the cytochemical precipitate area to the overall area of each mitochondrion was evaluated on COX-positive organelles to estimate the inner mitochondrial membrane fraction actively involved in cellular respiration. Following apoptotic stimulus, the whole mitochondrial population showed a significant increase of Nv and Vv, while V was significantly decreased. In COX-positive organelles higher values of Nv were found, V appeared significantly reduced, and Vv was unchanged. R was increased at a nonsignificant extent in apoptotic cells. COX-positive mitochondria accounted for 21% and 35% of the whole population in control and in apoptotic cells, respectively. These findings document that in the early stages of apoptosis the increased fraction of small mitochondria provides an adequate amount of ATP for progression of the programmed cell death and these more efficient organelles appear to represent a reactive response to the loss of metabolically impaired mitochondria. A better understanding of the mitochondrial role in neuronal apoptosis may suggest potential interventions to prevent the extensive nerve cell death typical of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Abstract: The effects of acute administration of two benzodiazepines and a non-benzodiazepine hypnotic on behavior and brain metabolism were evaluated in rats. After testing the behavioral action of the benzodiazepines on the open field and the elevated plus-maze, the effects of the three drugs on neuronal metabolism of particular limbic regions were measured using cytochrome c oxidase (CO) histochemistry. Diazepam (5 mg/kg i.p.) and alprazolam (0.5 mg/kg i.p.) induced clear anxiolytic effects and a decrease in locomotion, whereas zolpidem (2 mg/kg i.p.) caused an intense hypnotic effect. The anxiolytic effects of alprazolam were distinguishable from diazepam due to the pharmacological and clinical profile of this triazolobenzodiazepine. CO activity decreased significantly in almost all the limbic regions evaluated after zolpidem administration. However, significant prominent decreases in CO activity were found after diazepam treatment in the medial mammillary nucleus, anteroventral thalamus, cingulate cortex, dentate gyrus and basolateral amygdala. Alprazolam caused similar decreases in CO activity, with the exception of the prelimbic and cingulate cortices, where significant increases were detected. In agreement with previous studies using other functional mapping techniques, our results indicate that particular benzodiazepines and non-benzodiazepine hypnotics induce selective changes in brain oxidative metabolism. [Copyright &y& Elsevier]

Synaptic mitochondria, cytochemically positive to cytochrome oxidase (COX) activity, were investigated by morphometric methods in the hippocampal dentate gyrus of adult and old rats. The number of mitochondria/microm(3) of tissue (Nv), the volume fraction occupied by mitochondria/microm(3) of tissue (Vv), the average mitochondrial volume (V), the longer mitochondrial diameter (F(max)), and the ratio R:mitochondrial area/overall area of the cytochemical precipitate due to COX activity were measured on COX-positive organelles. In old animals, Nv, Vv, V, and F(max) increased at a not significant extent; R was not significantly decreased. The complement (%) of longer organelles was higher in old animals. COX activity is currently considered an endogenous marker of neuronal oxidative metabolism; thus, although our findings refer to the discrete subpopulation of COX-positive organelles located at synaptic terminals, they support that changes of mitochondrial ultrastructure and metabolic competence may contribute to the age-related alterations of neuronal performances. [ABSTRACT FROM AUTHOR]

Cytochemically evidenced cytochrome oxidase activity was morphometrically measured in the cerebellar cortex of adult and old rats. The ratio (R) between the area of the precipitate due to the cytochemical reaction and the overall area of each mitochondrion was calculated. While in adult rats an inverse correlation between mitochondrial size and R values (r = -.905) was envisaged, in old animals increasing values of R were paired by increases in mitochondrial area (r =.561). Paired-quartile comparisons of the R values from adult and old animals documented a marked age-related impairment of the mitochondrial metabolic competence in small (I quartile: -31.6%) and medium-sized (II quartile: -26.4; III quartile: -16.4) mitochondria, while large organelles showed the lowest age-related decrease (IV quartile: -3.0%). The present findings support that a marked dysfunction of small and medium-sized mitochondria contributes to the significant decay of energy metabolism currently reported in physiological aging. [ABSTRACT FROM AUTHOR]